Inhibition of EGFR Signaling by N-cyclohexyl-2-(1-(phenylsulfonyl)piperidin-4-yl) acetamide
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.org..
BACKGROUND: The epidermal growth factor receptor (EGFR) is a driver oncogene and specific blockade of EGFR has been shown to be an effective therapeutic approach against multiple human cancers.
AIMS: Here we employed the homogeneous time-resolved fluorescence (HTRF) technology to screen new EGFR mediators.
METHOD: 4 hits (NDS-41107, NDS-41119, NDS-41111 and NDS-41126) were confirmed in a compound library of 8000 compounds, and the IC50 values were determined to be 15.45±2.25µM (NDS-41107), 6.16±0.88 µM (NDS-41119), 11.33±3.31 µM (NDS-41111) and 11.19±1.67µM (NDS-41126), respectively. We then showed that NDS-41119 (N-cyclohexyl-2-(1-(phenylsulfonyl) piperidin-4-yl) acetamide) significantly inhibited EGFR signaling in human lung cancer cells, as evidenced by decreased phosphorylation of EGFR、ERK and Akt. NDS-41119 also attenuated EGF-induced cell proliferation and migration in a dose-dependent manner. We finally demonstrated that NDS-41119 inhibited the T790M mutation in NCI-H1975 cells and potentiated the effect of gefitinib against resistant cells.
RESULT: Our results will contribute to the development of novel EGFR-targeted anti-cancer drugs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Anti-cancer agents in medicinal chemistry - 17(2017), 11 vom: 24. Nov., Seite 1500-1507 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lin, Sensen [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.12.2017 Date Revised 02.12.2018 published: Print Citation Status MEDLINE |
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| doi: |
10.2174/1871520617666170327125251 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM270444564 |
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| 245 | 1 | 0 | |a Inhibition of EGFR Signaling by N-cyclohexyl-2-(1-(phenylsulfonyl)piperidin-4-yl) acetamide |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.org. | ||
| 520 | |a BACKGROUND: The epidermal growth factor receptor (EGFR) is a driver oncogene and specific blockade of EGFR has been shown to be an effective therapeutic approach against multiple human cancers | ||
| 520 | |a AIMS: Here we employed the homogeneous time-resolved fluorescence (HTRF) technology to screen new EGFR mediators | ||
| 520 | |a METHOD: 4 hits (NDS-41107, NDS-41119, NDS-41111 and NDS-41126) were confirmed in a compound library of 8000 compounds, and the IC50 values were determined to be 15.45±2.25µM (NDS-41107), 6.16±0.88 µM (NDS-41119), 11.33±3.31 µM (NDS-41111) and 11.19±1.67µM (NDS-41126), respectively. We then showed that NDS-41119 (N-cyclohexyl-2-(1-(phenylsulfonyl) piperidin-4-yl) acetamide) significantly inhibited EGFR signaling in human lung cancer cells, as evidenced by decreased phosphorylation of EGFR、ERK and Akt. NDS-41119 also attenuated EGF-induced cell proliferation and migration in a dose-dependent manner. We finally demonstrated that NDS-41119 inhibited the T790M mutation in NCI-H1975 cells and potentiated the effect of gefitinib against resistant cells | ||
| 520 | |a RESULT: Our results will contribute to the development of novel EGFR-targeted anti-cancer drugs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a EGFR | |
| 650 | 4 | |a HTRF | |
| 650 | 4 | |a cell migration | |
| 650 | 4 | |a cell proliferation | |
| 650 | 4 | |a gefitinib. | |
| 650 | 4 | |a lung cancer | |
| 650 | 7 | |a Acetamides |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a N-cyclohexyl-2-(1-(phenylsulfonyl)piperidin-4-yl)acetamide |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a Sulfonamides |2 NLM | |
| 650 | 7 | |a EGFR protein, human |2 NLM | |
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| 650 | 7 | |a ErbB Receptors |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 700 | 1 | |a Li, Hang |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Luyong |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hongyang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xinxin |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Shengtao |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Li |e verfasserin |4 aut | |
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